Increased Growth Hormone Binding to Liver Membranes of Obese Zucker Rats

Description of the recessive, homozygote obese Zucker rat (fafa) includes disorders of growth and reproduction. The aim of this study was to compare responsiveness of adenohypophyseal cells, obtained from male fafa rats and from their lean siblings, to growth hormone-releasing factor (GRF) and to luteinizing hormone-releasing hormone (LHRH). Pituitary cells were cultured for 4 days and were then challenged with either GRF-29 (the NH2-terminal 29 amino acid GRF peptide that expresses full biological activity of its parent 44 amino acid molecule) or [D-Trp6]LHRH (LHRH-A, an LHRH agonist). Medium was assayed for growth hormone (GH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) by radioimmunoassay. Dose-response curves were compared using the computer program ALLFIT. The median effective GRF-29 concentration (EC50) computed for hypophyseal cells cultured from lean animals (0.30 +/- 0.01 fM; means +/- SE of 4 experiments) was less (P less than 0.01) than that calculated for cells obtained from fafa rats (15.8 +/- 6.7 fM). In contrast, cells derived from lean littermates required a larger (EC50) concentration of LHRH-A than did gonadotrophs cultured from obese rats [58.2 +/- 1.2 vs. 10.7 +/- 1.2 pM (P less than 0.01) and 59.4 +/- 10.4 vs. 15.7 +/- 7.6 pM (P less than 0.05)] to secrete LH and FSH, respectively. Our data describe an attenuated pituitary response to GRF-29 and an enhanced response to LHRH-A in the fafa.

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Pituitary regulation of human growth hormone binding sites in rat liver membranes

Metabolism ◽

10.1016/0026-0495(76)90092-5 ◽

1976 ◽

Vol 25 (3) ◽

pp. 341-353 ◽

Cited By ~ 36

Author(s):

A.C. Herington ◽

L.S. Phillips ◽

W.H. Daughaday

Keyword(s):

Growth Hormone ◽

Rat Liver ◽

Human Growth Hormone ◽

Binding Sites ◽

Human Growth ◽

Hormone Binding ◽

Liver Membranes

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Mechanisms of Impaired Growth Hormone Secretion in Genetically Obese Zucker Rats: Roles of Growth Hormone-Releasing Factor and Somatostatin*

Endocrinology ◽

10.1210/endo-127-6-3087 ◽

1990 ◽

Vol 127 (6) ◽

pp. 3087-3095 ◽

Cited By ~ 41

Author(s):

GLORIA SHAFFER TANNENBAUMt ◽

MARTINE LAPOINTE ◽

WENDY GURD ◽

JUDITH A. FINKELSTEIN

Keyword(s):

Growth Hormone ◽

Hormone Secretion ◽

Growth Hormone Secretion ◽

Zucker Rats ◽

Growth Hormone Releasing Factor ◽

Obese Zucker Rats

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Obesity-Associated Decrease in Growth Hormone-Releasing Hormone Gene Expression: A Mechanism for Reduced Growth Hormone mRNA Levels in Genetically Obese Zucker Rats

Neuroendocrinology ◽

10.1159/000126558 ◽

1993 ◽

Vol 58 (3) ◽

pp. 332-337 ◽

Cited By ~ 22

Author(s):

Iqbal Ahmad ◽

Judith A. Finkelstein ◽

Thomas R. Downs ◽

Lawrence A. Frohman

Keyword(s):

Gene Expression ◽

Growth Hormone ◽

Zucker Rats ◽

Mrna Levels ◽

Growth Hormone Releasing Hormone ◽

Releasing Hormone ◽

Growth Hormone Mrna ◽

Obese Zucker Rats

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THE PRESENCE OF LACTOGEN BUT NOT GROWTH HORMONE BINDING SITES IN THE ISOLATED RAT HEPATOCYTE

Journal of Endocrinology ◽

10.1677/joe.0.0740323 ◽

1977 ◽

Vol 74 (2) ◽

pp. 323-334 ◽

Cited By ~ 15

Author(s):

A. C. HERINGTON ◽

N. M. VEITH

Keyword(s):

Growth Hormone ◽

Amino Acid ◽

Binding Sites ◽

Specific Binding ◽

Female Rats ◽

Scatchard Analysis ◽

Hormone Binding ◽

Binding Studies ◽

Membrane Function ◽

Liver Membranes

The binding of 125I-labelled human growth hormone (hGH) and bovine growth hormone (bGH) has been studied in hepatocytes isolated from female rats by perfusion with collagenase in situ. The cells appeared to retain normal membrane function, in that amino acid ([14C]α-aminoisobutyric acid) transport was both saturable and temperature-dependent. Amino acid ([14C]leucine) incorporation into protein was also linear over 3 h and was inhibited by cycloheximide. Binding of 125I-labelled hGH was dependent on time, temperature, hepatocyte concentration and hGH concentration. At 22 °C, binding reached a steady-state after 2·5 h and had a half-life of dissociation of 2–3 h. Hormone specificity studies indicated that binding was specific for hormones with prolactin-like activity (hGH, prolactins) and not for growth hormones themselves (bGH). Scatchard analysis revealed a single class of binding site with a binding capacity of 26·74 ± 3·73 fmol/106 cells and a binding affinity of 1·24 × 109 ± 0·17 × 109 (s.e.m.) l/mol (n = 10). There was a significant sex difference in binding (female > male) and binding was subject to marked regulation by oestrogens (stimulation of binding) and by androgens (inhibition). The lactogen-binding sites, therefore, were comparable in many respects to those previously reported in rat liver membranes. No distinct GH binding sites were demonstrable as shown by the lack of specific binding by 125I-labelled bGH, purified either by Sephadex chromatography or by binding to and elution from GH receptors in rabbit liver membranes. The value of receptor purification of tracer for use in hormone binding studies was indicated by a substantial lowering of non-specific binding.

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